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NK cell-based immunotherapies against tumors

  • Review Article
  • Published:
Central European Journal of Medicine

Abstract

Natural killer (NK) cells provide the first line of defence against pathogens and tumors. Their activation status is regulated by pro-inflammatory cytokines and by ligands that either target inhibitory or activating cell surface receptors belonging to the immunoglobulin-like, C-type lectin or natural cytotoxicity receptor families. Apart from non-classical HLA-E, membrane-bound heat shock protein 70 (Hsp70) has been identified as a tumor-specific recognition structure for NK cells expressing high amounts of the C-type lectin receptor CD94, acting as one component of an activating heterodimeric receptor complex. Full-length Hsp70 protein (Hsp70) or the 14-mer Hsp70 peptide T-K-D-N-N-L-L-G-R-F-E-L-S-G (TKD) in combination with pro-inflammatory cytokines enhances the cytolytic activity of NK cells towards Hsp70 membrane-positive tumors. Based on these findings cytokine/TKD-activated NK cells were adoptively transferred in tumor patients. These findings were compared to results of clinical trials using cytokine-activated NK cells.

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Abbreviations

AML:

Acute myelogenous leukemia

APC:

Antigen presenting cells

GrB:

Granzyme B

GvHD:

Graft-versus-host disease

GvL:

Graft versus leukemia

HLA:

Human leukocyte antigen

HSP:

Heat shock protein(s)

MHC:

Major histocompatibility complex

NF-κB:

Nuclear factor-kappaB

NK cell:

Natural killer cell

IFN-γ:

Interferon-gamma

IL-2(15):

interleukin-2

PBL:

Peripheral blood lymphocytes

TNF-α:

Tumor necrosis factor-alpha

TLR:

Toll-like receptor(s)

ULBP:

UL-16 binding protein(s)

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  1. Institute of Medical Biochemistry and Molecular Biology, University of Greifswald, Clinical Center Sauerbruchstraße, D-17487, Greifswald, Germany

    Jürgen Radons

  2. Department of Hematology and Internistic Oncology, University Hospital of Regensburg, D-93053, Regensburg, Germany

    Stefan Stangl & Gabriele Multhoff

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Radons, J., Stangl, S. & Multhoff, G. NK cell-based immunotherapies against tumors. cent.eur.j.med 1, 179–204 (2006). https://doi.org/10.2478/s11536-006-0023-x

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